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- Publisher Website: 10.1073/pnas.0806341105
- Scopus: eid_2-s2.0-57449111690
- PMID: 19011089
- WOS: WOS:000261489300049
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Article: A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization
Title | A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization | ||||||
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Authors | |||||||
Keywords | Adipose tissue Insulin resistance Obesity Yeast 2-hybrid system | ||||||
Issue Date | 2008 | ||||||
Publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org | ||||||
Citation | Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18302-18307 How to Cite? | ||||||
Abstract | Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFα. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders. © 2008 by The National Academy of Sciences of the USA. | ||||||
Persistent Identifier | http://hdl.handle.net/10722/163218 | ||||||
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 | ||||||
ISI Accession Number ID |
Funding Information: We thank Dr. Wenhong Cao (The Hamner Institute for Health Science, Research) for providing WAT from ND- or HFD-fed mice. This work wassupported by grants from the National Institutes of Health (DK76902, to F.L.; and DK69930, to L.Q.D.) and Hong Kong Research Grant Council (CRF 2/07C, to AX). | ||||||
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Liu, M | en_US |
dc.contributor.author | Zhou, L | en_US |
dc.contributor.author | Xu, A | en_US |
dc.contributor.author | Lam, KSL | en_US |
dc.contributor.author | Wetzel, MD | en_US |
dc.contributor.author | Xiang, R | en_US |
dc.contributor.author | Zhang, J | en_US |
dc.contributor.author | Xin, X | en_US |
dc.contributor.author | Dong, LQ | en_US |
dc.contributor.author | Liu, F | en_US |
dc.date.accessioned | 2012-09-05T05:28:50Z | - |
dc.date.available | 2012-09-05T05:28:50Z | - |
dc.date.issued | 2008 | en_US |
dc.identifier.citation | Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18302-18307 | en_US |
dc.identifier.issn | 0027-8424 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/163218 | - |
dc.description.abstract | Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFα. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders. © 2008 by The National Academy of Sciences of the USA. | en_US |
dc.language | eng | en_US |
dc.publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org | en_US |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | en_US |
dc.subject | Adipose tissue | - |
dc.subject | Insulin resistance | - |
dc.subject | Obesity | - |
dc.subject | Yeast 2-hybrid system | - |
dc.subject.mesh | 3T3-L1 Cells | en_US |
dc.subject.mesh | Adiponectin - Chemistry - Metabolism - Secretion | en_US |
dc.subject.mesh | Adult | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Biocatalysis | en_US |
dc.subject.mesh | Biopolymers - Chemistry | en_US |
dc.subject.mesh | Case-Control Studies | en_US |
dc.subject.mesh | Electrophoresis, Polyacrylamide Gel | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Glutathione Transferase - Metabolism - Physiology | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mice, Inbred Balb C | en_US |
dc.subject.mesh | Middle Aged | en_US |
dc.subject.mesh | Molecular Chaperones - Metabolism - Physiology | en_US |
dc.subject.mesh | Obesity - Metabolism | en_US |
dc.subject.mesh | Protein Folding | en_US |
dc.subject.mesh | Protein Processing, Post-Translational | en_US |
dc.subject.mesh | Rna Interference | en_US |
dc.subject.mesh | Transcription, Genetic | en_US |
dc.subject.mesh | Two-Hybrid System Techniques | en_US |
dc.title | A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization | en_US |
dc.type | Article | en_US |
dc.identifier.email | Xu, A:amxu@hkucc.hku.hk | en_US |
dc.identifier.email | Lam, KSL:ksllam@hku.hk | en_US |
dc.identifier.authority | Xu, A=rp00485 | en_US |
dc.identifier.authority | Lam, KSL=rp00343 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1073/pnas.0806341105 | en_US |
dc.identifier.pmid | 19011089 | en_US |
dc.identifier.scopus | eid_2-s2.0-57449111690 | en_US |
dc.identifier.hkuros | 154211 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-57449111690&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 105 | en_US |
dc.identifier.issue | 47 | en_US |
dc.identifier.spage | 18302 | en_US |
dc.identifier.epage | 18307 | en_US |
dc.identifier.isi | WOS:000261489300049 | - |
dc.publisher.place | United States | en_US |
dc.identifier.f1000 | 1131889 | - |
dc.identifier.scopusauthorid | Liu, M=16233590900 | en_US |
dc.identifier.scopusauthorid | Zhou, L=35274069900 | en_US |
dc.identifier.scopusauthorid | Xu, A=7202655409 | en_US |
dc.identifier.scopusauthorid | Lam, KSL=8082870600 | en_US |
dc.identifier.scopusauthorid | Wetzel, MD=36003271800 | en_US |
dc.identifier.scopusauthorid | Xiang, R=7006818699 | en_US |
dc.identifier.scopusauthorid | Zhang, J=22735803600 | en_US |
dc.identifier.scopusauthorid | Xin, X=36872878400 | en_US |
dc.identifier.scopusauthorid | Dong, LQ=7402561181 | en_US |
dc.identifier.scopusauthorid | Liu, F=36064205800 | en_US |
dc.identifier.issnl | 0027-8424 | - |